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is a hallmark of CF, and whether there is an inherent defect in CF that predisposes to excessive inflammation is controversial. Several genes involved in inflammation and the immune system are located in the regions of the markers identified: TNF superfamily members Tnfsf4, 6, and 8 (chr.1, 84.9–85 cM) which are involved in T cell activation [37,38]; three selectin genes (Sele, Sell, Selp, chr.1, 86.6 cM) which are involved in immune cell infiltration into inflamed tissues [39]; several members of immune cell surface proteins of the Slam family (slamf1, 2, 5, 6, and 9; chr.1, 89.5–93.3 cM) [40]; the chemokine gene Xcl1 (chr.1, 87 cM) which is expressed by mast cells and recruits lymphocytes [41]; several immunoglobulin Fc receptor genes (Fcrl3, Fcgr2b, and Fcgr3 at chr.1, 92.3 cM; Fcer1g at chr.1, 93.3 cM; Fcer1a at chr.1, 94.2 cM); the flagellin receptor Tlr5 (chr.1, 98 cM); Mmp3 (chr.9, 1 cM) which recruits CD4+ lymphocytes [42]; Mmp7 (chr.9, 1 cM) which activates Paneth cell-derived cryptdins (α-defensins) [43]; Icam1 (chr.9, 7 cM) which is involved in lymphocyte infiltration into inflamed tissues [44]; Kitl (chr.10, 57 cM) which is also known as stem cell factor, and is crucial for mast cell differentiation [45]; Im5 (chr.10, 65 cM) which is involved in antibody-responsiveness [46]; Lyzs (chr.10, 66 cM) which is a Paneth cell product that digests cell walls of bacteria [47]; Ifng (chr.10, 67 cM) which is an important inflammatory signal in CF as well as other conditions [48]; Il22 (chr.10, 67 cM), a member of the anti-inflammatory IL-10 interleukin family [49]; and the Stat2 and 6 genes (chr.10, 70 cM) which are important components of intracellular signaling pathways [50]."}

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